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How medical cannabis interacts with the endocannabinoid system

Juicy Fields breaks down everything you need to know about the endocannabinoid system and how cannabis components interact with it.

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Juicy Fields: How medical Cannabis Interacts with the endocannabinoid system

The advent of medical marijuana legalisation has been well appreciated over the past decade. But since the early 1960s, researchers have been working around the clock to bring out the benefits of medical marijuana. And currently, some of the discoveries made over the years have made a huge impact in the quest to understand medical cannabis and its importance to general human health.

All animals, including humans, have an internal network system consisting of lipids, enzymes, and receptors that help maintain an internal bodily balance, aka homeostasis. This includes how each person responds to cannabis.

That complex internal system is called the endocannabinoid system (ECS), which was discovered in the late 1980s by medical experts exploring THC – the chemical compound in marijuana that causes a ‘high.’

Lots of studies have been going on to try and understand how the ECS interacts and responds to cannabinoids and other cannabis compounds. What is known is that the ECS helps regulate several physiological processes like sleep, appetite, fertility/reproduction, mood, and memory.

But what is there to know about how medical marijuana affects or influences the endocannabinoid system? Well, this read breaks down everything you need to know about the ECS and how cannabis components interact with it.

Understanding the ECS and How it Works

In addition to the mentioned physiological processes that ECS is responsible for, it plays a major role in immune system regulation, sensory integration, neural development, and several cardiovascular processes. The ECS is an endogenous system that consists of components that interact with the delta-9-THC variant, a major component of the cannabis plant.

There are three major components of the Endocannabinoid System;

  • Endocannabinoids
  • Regulatory enzymes
  • Receptors.

Understanding how the three ECS components work will help us grasp their role when interacting with medical cannabis. Let’s dissect each one in brief.

Endocannabinoids

Endocannabinoids are also commonly referred to as endogenous cannabinoids. Just as the name endo has it, they are cannabinoid compounds produced by our bodies. They are the same as the cannabinoids from marijuana, only that these originate from our bodies. According to research, there are two types of endocannabinoids;

  • Anandamide AEA (scientifically termed as N-arachidonoylethanolamine)
  • 2-AG or 2-arachidonoylglycerol

The two endocannabinoids play a major role in maintaining bodily homeostasis, and they are produced and synthesized on demand.

Regulatory enzymes

The ECS also has enzymes whose main function is to digest and break down endocannabinoids after they have finished their role. They also metabolize consumed cannabinoids in case a person consumes cannabis. The two main enzymes include fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). FAAL is responsible for synthesizing anandamide and THC, while MAGL breaks down 2-AG.

These inhibit the accumulation of harmful endocannabinoids and phytocannabinoids in the body. Phytocannabinoids are cannabis-specific chemical compounds found in the cannabis plant that interact with ECS receptors. THC and Cannabidiol (CBD) are good examples of these phytocannabinoids. High doses of these cannabinoids can be dangerous, and that’s where the ECS enzymes come in to help maintain the perfect balance.

Endocannabinoid receptors

Every human cell has cannabinoid receptors that form the central nervous system (CNS) and the peripheral nervous system (PNS) framework. Endocannabinoids bind on these receptors and send signals to the ECS when action needs to be taken. There’s a wide range of receptors all over the CNS and the PNS like the CB1 and CB2 receptors, Opioid receptors, GPR55 receptors, serotonin receptors, and dopamine receptors. But we’ll focus on the CB1 and CB2 receptors.

CB1s (Cannabinoid Receptor 1) are found in the central nervous system. Cannabinoids interact with the brain through CB1 receptors. THC and other psychoactive “high” molecules attach to CB1 receptors in the brain. The cannabinoids that bind to CB1 receptors can slow down the release of Glutamate or GABA (gamma-aminobutyric acid). While glutamate stimulates the neurological system, GABA calms it down.

GABA levels are usually low when glutamate levels are high, and vice versa. When receptors detect the presence of THC, it blocks the production of GABA. Inhibiting GABA production could cause an increase in dopamine levels circulating the body, which then causes the psychoactive ‘high’ effect.

CB2 receptors, on the other hand, are found in the peripheral nervous system, the gastrointestinal system, and part of the neurons in the brain. CB2 receptors have been linked to immunological suppression, apoptosis (cell death), and the activation of cell migration and development, according to research. People with malignant tumors and precancerous cells may benefit from these results.

CB2 receptor agonists also have anti-inflammatory characteristics that are useful in treating pain and inflammation. Research has also shown that CB2 receptors could majorly treat autoimmune illnesses, including arthritis.

THC and the endocannabinoid system

As we’d mentioned earlier, THC is the chemical compound in cannabis responsible for most of the psychoactive effects associated with marijuana.

THC, like endocannabinoids, interacts with your ECS by attaching to receptors once within your body. Its potency stems from the fact that it binds to both CB1 and CB2 receptors. This enables it to have various physiological and psychological effects, some of which are more favorable than others.

THC, for example, can help with pain relief and appetite stimulation. However, in certain situations, it might lead to paranoia and worry. There’s ongoing medical research on whether scientists can produce synthetic THC cannabinoids that positively affect the ECS.

Companies like JuicyFields are working on promoting the medical benefits of THC (wrongly associated with exclusive recreational use) by creating a crowdgrowing platform to boost the production of medical cannabis with high THC content.

CBD and the endocannabinoid system

Cannabidiol (CBD) is the second major cannabinoid found in the Cannabis plant, which doesn’t cause a ‘high’ like THC. Medical results have shown that CBD has zero to minimum negative effects on users.

Though it’s not yet completely certain how CBD interacts with the ECS, the available study results so far have shown that it doesn’t bind to CB1 and CB2 in the same way that THC does. CBD, according to most experts, inhibits the breakdown of endocannabinoids. As a result, they can have a greater impact on your body. Others think CBD binds to an unidentified receptor.

While the exact mechanism of CBD’s action remains unknown, research suggests that it can assist with pain relief, inflammation, nausea, and other symptoms linked with various illnesses.

Take away

The ECS is critical to maintaining the stability of your internal functions. We still don’t know much about it, though.

There’s yet to be a comprehensive study and tangible results on how medical cannabinoids like CBD impact the ECS and how helpful that would be when prescribing medical marijuana.

As scientists get a greater knowledge of the ECS, it may one day hold the key to curing a host of conditions.

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How THC and CBD work together in the brain – new study

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How THC and CBD work together in the brain – new study

New findings on how CBD and THC – the psychoactive compound in cannabis – affect the brain when administered together, could help to develop new cannabinoid therapeutics, scientists say.

A study has investigated the impact on the brain of CBD and THC, both as separate entities and when co-administered.

Researchers at University College London (UCL) analysed data from previous studies, including one which used functional Magnetic Resonance Imaging (fMRI) technology to measure brain activity in participants taking CBD and THC.

For the first time, they explored the response of the striatum region of the brain – a major part of the motor and reward systems. This is a critical component of numerous aspects of cognition, including motor and action planning, decision-making and motivation.

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One study compared inhaled cannabis containing 8 mg THC, 8 mg THC + 10 mg CBD and a placebo. It showed strong disruptive effects of both THC and THC + CBD on connectivity in the associative and sensorimotor networks.

However it also identified a “specific effect of THC” in the limbic striatum network which was not present in the THC + CBD condition.

In a second study, testing oral 600 mg CBD versus placebo, CBD increased connectivity in the associative network, but produced only relatively minor disruptions in the limbic and sensorimotor networks.

The study concludes that THC “strongly disrupts striato-cortical networks” but that this effect is mitigated by the co-administration of CBD.

It states: “Oral CBD administered has a more complex effect profile of relative increases and decreases in connectivity.

“The insula [part of the brain implemented in diverse functions including emotions and self-awareness] emerges as a key region affected by cannabinoid-induced changes in functional connectivity, with potential implications for understanding cannabis-related disorders, and the development of cannabinoid therapeutics.”

This is the first report in human subjects of data from THC, THC + CBD and CBD use achieved “using a unified set of analysis methods, and with all comparisons performed in a placebo-controlled, double-blind design”.

Read the full report here.

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Five new cannabis studies to have on your radar

The latest scientific papers exploring cannabis and its impact on health and society.

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Five new cannabis studies to have on your radar

Get up to date with the latest cannabis-related research from across the globe.

Over the past few weeks, we’ve seen papers published around inaccurate labelling, the effects of cannabis on Covid-19, the impact of legalisation in Uruguay and how cannabis users might require more sedation during medical procedures.

Read on for five significant studies to dive into.

Lower Covid-19 severity among cannabis users

A recent study has discovered an association between lower Covid-19 severity and cannabis use among hospitalised patients.

The researchers aimed to assess whether current cannabis users hospitalised for Covid-19 had different outcomes compared to non-users through a retrospective analysis of 1,831 patients admitted to UCLA Medical Centre in California.

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Analysis of the data found that cannabis users had significantly better outcomes compared to non-users, shorter hospitalisation, lower ICU admission rates and less need for mechanical ventilation.

Interestingly, the researchers also found that active users had lower levels of inflammatory markers upon admission than non-users.

The authors of the study concluded: “This retrospective cohort study suggests that active marijuana users hospitalised with COVID-19 had better clinical outcomes compared with non-users. However, our results need to be interpreted with caution given the limitations of a retrospective analysis.

“Prospective and observational studies will better help elucidate the effects of marijuana use in COVID-19 patients.”

Cannabis users require more sedation for endoscopy

According to new research, patients who use cannabis required higher levels of sedation during gastric endoscopies than non-users.

As cannabis is legalised in more places and usage continues to rise, researchers in Canada said clinicians should be aware of patients’ cannabis consumption and prepare themselves for increased sedation and the risks that come with it.

The authors of the study conducted a prospective cohort study of 419 adult outpatients undergoing endoscopic procedures at three Canadian centres. Procedures were conducted under conscious sedation, which leaves the patient relaxed and comfortable but partially conscious during the procedure.

Cannabis use was associated with increased odds of requiring higher total sedation during gastroscopy, an endoscopic procedure that begins with the insertion of a tube and camera through the throat.

Legalisation not associated with increased cannabis use among young people

A recent study from researchers in Uruguay found that the use of cannabis following legalisation decreased among teenagers.

Uruguay was the first country in the world to legalise and regulate recreational cannabis. Since legalising the drug in 2016, the country is now regarded as a pioneer, paving the way for other countries like Canada, Mexico and Malta.

Using data from cross-sectional surveys of secondary students in Uruguay and Chile, the study evaluated changes in the prevalence of past-year, past-month and any risky and frequent cannabis use following the enactment and implementation of cannabis legalisation

“The legalisation of recreational cannabis in Uruguay was not associated with overall increases in either past-year/past-month cannabis use or with multi-year changes in any risky and frequent cannabis use among young people,” the authors stated in the paper’s abstract.

Current cannabis labelling system “doesn’t tell you much”

Labels like indica, sativa and hybrid—commonly used to distinguish one category of cannabis from another—tell consumers little about what’s in their product and could be confusing or misleading, suggests a new study of nearly 90,000 samples across six states in America.

Published on 19 May in the journal PLOS One, the research constitutes the largest analysis to date of the chemical composition of cannabis products.

It finds that commercial labels “do not consistently align with the observed chemical diversity” of the product. The authors are now calling for a “weed labelling system” akin to the Food and Drug Administration’s “nutrition facts panel” for food.

“Our findings suggest that the prevailing labelling system is not an effective or safe way to provide information about these products,” said co-author Brian Keegan, an assistant professor of Information Science at CU Boulder.

“This is a real challenge for an industry that is trying to professionalise itself.”

Cannabis dependence treatment is effective in tackling common co-morbidities

Earlier this month, Australian researchers released a paper looking into the effectiveness of cannabis dependency treatment on common co-morbidities, including mood, sleep and pain problems.

The researchers found that the treatment helped decrease anxiety, stress and sleep disturbance among the cohort of 128 cannabis-dependent participants.

The analysis used data from a 12-week double-blind placebo-controlled trial testing the effectiveness of the cannabis-based medicine nabiximols against placebo in reducing illicit cannabis use.

The researchers found that there was “no evidence” that nabiximols treatment is a barrier to reducing co-morbid symptoms. In fact, they found that the treatment reduced illicit cannabis use and improved comorbidity symptoms, even when participants were not able to achieve abstinence.

 

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Research finds cannabis consumers may require more sedation

Consumers required higher levels of sedation during endoscopic procedures than non-users

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Research finds cannabis consumers may require more sedation

Experts have highlighted the need for doctors to be more aware of their patients cannabis use, as research suggests consumers may require higher levels of sedation.

As cannabis is legalised in more places and usage continues to rise, researchers in Canada said clinicians should be aware of patients’ cannabis consumption, and prepare themselves for increased sedation and the risks that come with it.

It comes as a new study has associated cannabinoid use with increased odds of requiring higher total sedation during gastric endoscopies – a procedure that begins with the insertion of a tube and camera through the throat – than non-users.

The authors of the study conducted a prospective cohort study of 419 adult outpatients undergoing endoscopic procedures at three Canadian centres.

Procedures were conducted under conscious sedation, which leaves the patient relaxed and comfortable but partially conscious during the procedure.

US research programme studies cannabinoids in ovarian cancer

Researchers did not examine its impact on propofol sedation, which is more commonly used in the UK and US so more research would be needed to determine the wider impact of cannabis use on sedation.

“Patients didn’t have increased awareness or discomfort during procedures, but they did require more drugs,” said Yasmin Nasser, MD, PhD, lead researcher on the study and assistant professor at Snyder Institute for Chronic Diseases at the University of Calgary.

Each patient completed two questionnaires, one before the procedure about their cannabis use and another afterwards, indicating their awareness and comfort level during the procedure. The questionnaires were analysed along with details about the use of the sedatives midazolam, fentanyl and diphenhydramine during the procedure.

Cannabis use was associated with increased odds of requiring higher total sedation—defined as more than 5 mg of midazolam, or more than 100 mcg of fentanyl, or the need for diphenhydramine.

Interestingly, cannabis use was not associated with higher use of sedation during colonoscopy. Researchers said this could be because gastroscopy generally requires more sedation than colonoscopy due to the irritation caused in the upper part of the gastrointestinal tract.

Cannabinoid use was not independently associated with fentanyl use or adverse events, nor was it associated with intra-procedural awareness or discomfort, the authors found.

This study looked at whether patients were users or non-users of cannabis, but did not examine the timing, quantity or route of cannabis intake prior to the procedure. Researchers say these variables could be the basis for future studies.

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